Proof that MCT causes insulin resistance?

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Julie G
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Proof that MCT causes insulin resistance?

Postby Julie G » Sat Feb 03, 2018 3:17 pm

Hi friends, this feels too important to bury in another thread. I want to learn more. Searcher has shared a paper that proves MCT causes insulin resistance. I'd appreciate any thoughts.

Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation
https://academic.oup.com/jcem/article/97/1/208/2833397
Context:
Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling.
Objective:
We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance.
Design and Methods:
Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp.
Results:
MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (−28%, P = 0.003) and MCT/LCT (−20%, P < 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered.
Conclusions:
Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.

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Stavia
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Re: Proof that MCT causes insulin resistance?

Postby Stavia » Sat Feb 03, 2018 6:06 pm

Wow.
My thoughts
1. Mousies are not men and we should be very careful extrapolating mousie studies
2. We (humankind) don't really understand biochemistry fully
3. If I was drinking bulletproof coffee, I'd be considering my options and my insulin sensitivity carefully

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Re: Proof that MCT causes insulin resistance?

Postby Searcher » Sat Feb 03, 2018 6:28 pm

MCT is saturated fat.

More evidence (meta analysis of RCTs) about saturated fat and its impact on insulin resistance/glucose metabolism is here:

http://journals.plos.org/plosmedicine/a ... 02087-t002

Stavia, the study which Julie cited is a human study, not a mouse study. You're quite right to draw attention to the contrast with mouse studies.

The more we rely on scientific studies and the less we take the word of personalities, the safer will life become for APOE4 carriers. Science operates on reliable processes which continually correct errors. Personalities often have conflicts of interest, and tend to be slow to accept inconvenient facts. Sometimes that slowness compromises health outcomes among lay people.

My favorite thing about our community, apart from the obvious warmth and courtesy, is the openness to scientific processes, with constant refutation of error and increasingly clear understanding about how the human body and mind work. A reliance on scientific processes is the surest route to safety and wellbeing.

It's great that so much hard scientific evidence finds a place in our community.

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Re: Proof that MCT causes insulin resistance?

Postby Tincup » Sat Feb 03, 2018 8:42 pm

Simultaneously to the hyperinsulinemic-euglycemic clamp, a lipid emulsion was infused through a cannula in the contralateral arm. In the LCT condition, a 20% triglyceride emulsion (Intralipid; Fresenius Kabi, Bad Homburg, Germany) was infused at a rate of 1.3 ml/min for 6 h. This emulsion is based on soybean oil and consists of fatty acids longer than 16 carbon atoms or more (LCFA). Together with the lipid emulsion, heparin was coadministered (0.2 U/kg · min) to stimulate hydrolysis of the infused triglycerides, and subjects received a bolus injection of heparin (200 IU) upon the start of the test. In the MCT/LCT condition, a 20% triglyceride emulsion (Lipofundin; Braun Medical, Melsungen, Germany) was infused, together with a primed (200 IU) continuous (0.2 U/kg · min) infusion of heparin. In contrast to the LCT emulsion, 50% of the fatty acids present in the MCT/LCT emulsion were of medium chain length (≤12 carbon atoms), whereas the other 50% consisted of LCFA (≥16 carbon atoms), again derived from soybean oil. An infusion rate of 0.82 ml/min was used to match the plasma FFA levels obtained during the LCT clamp. This was established by pilot experiments. In the control condition, glycerol was infused to match the mean glycerol content of the lipid emulsions in the experimental conditions.


Not exactly like eating real food...
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apod
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Re: Proof that MCT causes insulin resistance?

Postby apod » Sun Feb 04, 2018 1:03 am

Looking at insulin sensitivity in muscle tissue following MCTs fed to "lean animals":

Contrasting metabolic effects of medium- versus long-chain fatty acids in skeletal muscle (2013)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826680/

"In conjunction with the increase in markers of mitochondrial metabolism, MCFAs also prevented lipid accumulation and insulin resistance in muscle, with similar glucose uptake and muscle triglyceride levels in MCFA-fed animals compared with lean animals fed a low-fat diet."

Examine.com writes:

"A small study involving 10 adults with type 2 diabetes reported significant increases in insulin sensitivity during a hyperinsulinemic-euglycemic clamp after four days of consuming 40 grams of MCTs prelative to shortening, which appeared to be owed to an increase in glucose uptake in peripheral tissues. However, a follow-up study in five free-living adults with type 2 diabetes reported that consuming 15 mL of MCTs with each of three meals per day for one month had no significant effect on fasting blood glucose, fasting insulin, or insulin sensitivity compared to corn oil, but did significantly lower the 3-hour average postprandial blood glucose response by ~44%. A 90 day randomized controlled trial using 18 grams of MCTs, relative to 18 grams of corn oil, in type 2 diabetics reported a 17% improvement in insulin sensitivity as assessed by HOMA-IR, while the control group experienced a worsening of sensitivty (7%); the difference between groups was significant."

There's also this one from 2016:
Medium-chain triglyceride ameliorates insulin resistance (and inflammation in high fat diet-induced obese mice):
https://www.ncbi.nlm.nih.gov/pubmed/25911003

And this one:

https://www.sciencedirect.com/science/a ... via%3Dihub

"MCFAs reduce lipoprotein secretion and attenuate postprandial triglyceride response. It was, however, frequently observed that MCTs increase fasting cholesterol and triglyceride levels. But, given in moderate amounts, in diets with moderate fat supply, MCFAs may actually reduce fasting lipid levels more than oils rich in mono- or polyunsaturated fatty acids. The same is true for glucose levels. MCTs improved several features contributing to enhanced insulin sensitivity."

I'm not quite sure what to make of it. In my experience, MCT increases glucose uptake, but this might be via higher insulin secretion which could be an issue if you were eating frequently or overweight.

I've also seen articles where BCAAs seem to be associated with insulin resistance.

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Re: RE: Re: Proof that MCT causes insulin resistance?

Postby Stavia » Sun Feb 04, 2018 3:59 am

Searcher wrote:MCT is saturated fat.

More evidence (meta analysis of RCTs) about saturated fat and its impact on insulin resistance/glucose metabolism is here:

http://journals.plos.org/plosmedicine/a ... 02087-t002

Stavia, the study which Julie cited is a human study, not a mouse study. You're quite right to draw attention to the contrast with mouse studies.

The more we rely on scientific studies and the less we take the word of personalities, the safer will life become for APOE4 carriers. Science operates on reliable processes which continually correct errors. Personalities often have conflicts of interest, and tend to be slow to accept inconvenient facts. Sometimes that slowness compromises health outcomes among lay people.

My favorite thing about our community, apart from the obvious warmth and courtesy, is the openness to scientific processes, with constant refutation of error and increasingly clear understanding about how the human body and mind work. A reliance on scientific processes is the surest route to safety and wellbeing.

It's great that so much hard scientific evidence finds a place in our community.
Searcher, it compared human outcome to mouse outcomes. And they had a surprising result.

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Re: Proof that MCT causes insulin resistance?

Postby Orangeblossom » Sun Feb 04, 2018 4:37 am

Isn't the main problem with IR sugar and high GI foods? Surely therefore it is those we need to worry about more than fats?

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Re: Proof that MCT causes insulin resistance?

Postby Searcher » Sun Feb 04, 2018 5:14 am

Orangeblossom wrote:Isn't the main problem with IR sugar and high GI foods? Surely therefore it is those we need to worry about more than fats?


Orange, you are wise to limit or even avoid foods with a high glycemic index.

However, an important cause of insulin resistance (IR) seems to be an excess of saturated fatty acids entering skeletal muscle, becoming incorporated into the lipid membranes of the endoplasmic reticulum, and stiffening those otherwise flexible membranes. The cells become less able to transport glucose out of the blood and into the cell.

Unsaturated fats counter this effect of saturated fatty acid on the endoplasmic reticulum membranes. They also counter the IR effect of saturated fats.

It seems sensible to replace saturated fats with "good fat" (unsaturated fat) to lower IR, among other important benefits of unsaturated fat.

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Re: Proof that MCT causes insulin resistance?

Postby Orangeblossom » Sun Feb 04, 2018 5:22 am

Searcher wrote:
Orangeblossom wrote:Isn't the main problem with IR sugar and high GI foods? Surely therefore it is those we need to worry about more than fats?


Orange, you are wise to limit or even avoid foods with a high glycemic index.

However, an important cause of insulin resistance (IR) seems to be an excess of saturated fatty acids entering skeletal muscle, becoming incorporated into the lipid membranes of the endoplasmic reticulum, and stiffening those otherwise flexible membranes. The cells become less able to transport glucose out of the blood and into the cell.

Unsaturated fats counter this effect of saturated fatty acid on the endoplasmic reticulum membranes. They also counter the IR effect of saturated fats.

It seems sensible to replace saturated fats with "good fat" (unsaturated fat) to lower IR, among other important benefits of unsaturated fat.



If you read this post, or are possibly referencing this study, you can see that is far from conclusive viewtopic.php?f=16&t=3961&p=46831&hilit=saturated+fat#p46831

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Re: Proof that MCT causes insulin resistance?

Postby Searcher » Sun Feb 04, 2018 6:13 am

Orange, the strongest level of evidence about saturated fat vs unsaturated fat, and insulin resistance/glucose metabolism, comes from randomized controlled trials. All such trials known were included in a meta-analysis, which was cited above in this thread.


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